                         SEQUENCE LISTING

<110>  Caribou Biosciences, Inc.
 
<120>  ENGINEERED CRISPR-CAS9 COMPOSITIONS AND METHODS OF USE

<130>  CBI017.30

<150>  62/202,715
<151>  2015-08-07

<150>  62/209,334
<151>  2015-08-24

<160>  128   

<170>  PatentIn version 3.5

<210>  1
<211>  31
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus pyogenes

<400>  1
caaaacagca uagcaaguua aaauaaggcu a                                      31


<210>  2
<211>  46
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus pyogenes

<400>  2
guccguuauc aacuugaaaa aguggcaccg agucggugcu uuuuuu                      46


<210>  3
<211>  33
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus thermophilus CRISPR-I

<400>  3
uaaaucuugc agaagcuaca acgauaaggc uuc                                    33


<210>  4
<211>  54
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus thermophilus CRISPR-I

<400>  4
augccgaaau caacacccug ucauuuuaug gcaggguguu uucguuauuu uuuu             54


<210>  5
<211>  32
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Listeria innocua

<400>  5
caaaauaaca uagcaaguua aaauaaggcu uu                                     32


<210>  6
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Listeria innocua

<400>  6
guccguuauc aacuuuuaau uaaguagcgc uguuucggcg cuuuuuuu                    48


<210>  7
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Neisseria meningitidis

<400>  7
cugcgaaaug agaaccguug cuacaauaag gccgucugaa                             40


<210>  8
<211>  56
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Neisseria meningitidis

<400>  8
aagaugugcc gcaacgcucu gccccuuaaa gcuucugcuu uaaggggcau cguuua           56


<210>  9
<211>  42
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus gallolyticus

<400>  9
uuggagcuau ucgaaacaac acagcgaguu aaaauaaggc uu                          42


<210>  10
<211>  50
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus gallolyticus

<400>  10
uguccguaca caacuuguaa aaguggcacc cgauucgggu gcguuuuuuu                  50


<210>  11
<211>  46
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Staphylococcus aureus

<400>  11
auuguacuua uaccuaaaau uacagaaucu acuaaaacaa ggcaaa                      46


<210>  12
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Staphylococcus aureus

<400>  12
augccguguu uaucucguca acuuguuggc gagauuuuu                              39


<210>  13
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Corynebacterium diphtheriae

<400>  13
agucacuaac uuaauuaaau agaacugaac cucaguaagc auuggcuc                    48


<210>  14
<211>  58
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Corynebacterium diphtheriae

<400>  14
guuuccaaug uugauugcuc cgccggugcu ccuuauuuuu aagggcgccg gcuuucuu         58


<210>  15
<211>  46
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Parvibaculum lavamentivorans

<400>  15
uagcaaaucg agaggcgguc gcuuuucgca agcaaauuga ccccuu                      46


<210>  16
<211>  77
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Parvibaculum lavamentivorans

<400>  16
gugcgggcuc ggcaucccaa ggucagcugc cgguuauuau cgaaaaggcc caccgcaagc       60

agcgcguggg ccuuuuu                                                      77


<210>  17
<211>  51
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Campylobacter lari

<400>  17
aauucuugcu aaagaaauuu aaaaagagac uaaaauaagu gguuuuuggu c                51


<210>  18
<211>  73
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Campylobacter lari

<400>  18
auccacgcag gguuacaauc ccuuuaaaac cauuaaaauu caaauaaacu agguuguauc       60

aacuuaguuu uuu                                                          73


<210>  19
<211>  50
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Neisseria cinerea

<400>  19
auugucgcac ugcgaaauga gaaccguugc uacaauaagg ccgucugaaa                  50


<210>  20
<211>  89
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Neisseria cinerea

<400>  20
agaugugccg caacgcucug ccccuuaaag cuucugcuuu aaggggcauc guuuauuucg       60

guuaaaaaug ccgucugaaa ccgguuuuu                                         89


<210>  21
<211>  47
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus pasteurianus

<400>  21
cuugcacggu uacuuaaauc uugcugagcc uacaaagaua aggcuuu                     47


<210>  22
<211>  43
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Derived from Streptococcus pasteurianus

<400>  22
augccgaauu caagcacccc auguuuugac augaggugcu uuu                         43


<210>  23
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  23
agtaataata cgactcacta tag                                               23


<210>  24
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  24
aagcaccgac tcggtgccac tttt                                              24


<210>  25
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  25
taatacgact cactatagtc cgttatcaac ttgaaaaagt ggcaccgagt cggtgctt         58


<210>  26
<211>  49
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  26
taatacgact cactatagca ggacagcata gcaagttgag ataaggcta                   49


<210>  27
<211>  49
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  27
tagccttatc tcaacttgct atgctgtcct gctatagtga gtcgtatta                   49


<210>  28
<211>  55
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  28
taatacgact cactataggg gccactaggg acaggatgtc tcagagctat gctgt            55


<210>  29
<211>  55
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  29
acagcatagc tctgagacat cctgtcccta gtggccccta tagtgagtcg tatta            55


<210>  30
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  30
ccccgttctc ctgtggattc                                                   20


<210>  31
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  31
atcctctctg gctccatcgt                                                   20


<210>  32
<211>  52
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  32
cactctttcc ctacacgacg ctcttccgat cttctggcaa ggagagagat gg               52


<210>  33
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  33
ggagttcaga cgtgtgctct tccgatctta tattcccagg gccggtta                    48


<210>  34
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  34
caagcagaag acggcatacg agattacgtg atgtgactgg agttcagacg tgtgctc          57


<210>  35
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  35
aatgatacgg cgaccaccga gatctacacc gtctaataca ctctttccct acacgacg         58


<210>  36
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  36
aatgatacgg cgaccaccga gatctacact ctctccgaca ctctttccct acacgacg         58


<210>  37
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  37
aatgatacgg cgaccaccga gatctacact cgactagaca ctctttccct acacgacg         58


<210>  38
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  38
aatgatacgg cgaccaccga gatctacact tctagctaca ctctttccct acacgacg         58


<210>  39
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  39
aatgatacgg cgaccaccga gatctacacc ctagagtaca ctctttccct acacgacg         58


<210>  40
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  40
aatgatacgg cgaccaccga gatctacacc tattaagaca ctctttccct acacgacg         58


<210>  41
<211>  62
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  41
ggcagtagcc ttatctcaac ttgctatgct gtcctgtttc caggacagca tagctctgag       60

ac                                                                      62


<210>  42
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  42
ggcagtagcc ttatctcaac                                                   20


<210>  43
<211>  63
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  43
taatacgact cactataggc aggtccgtta tcaacttgaa aaagtggcac cgagtcggtg       60

ctt                                                                     63


<210>  44
<211>  67
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  44
ggcagtgaac tagccttatc tcaacttgct atgctgtcct gtttccagga cagcatagct       60

ctgagac                                                                 67


<210>  45
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  45
ggcagtgaac tagccttatc                                                   20


<210>  46
<211>  68
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  46
taatacgact cactataggc agctaaggtc cgttatcaac ttgaaaaagt ggcaccgagt       60

cggtgctt                                                                68


<210>  47
<211>  56
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  47
taatacgact cactataggg gccactaggg acaggatgtc tcagagctat gctgtc           56


<210>  48
<211>  56
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  48
taatacgact cactatagtt tgtgtttcca taaactggtc tcagagctat gctgtc           56


<210>  49
<211>  56
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  49
taatacgact cactatagcc cgccaccacc aggatgtgtc tcagagctat gctgtc           56


<210>  50
<211>  56
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  50
taatacgact cactataggc agccagcatg atgagacgtc tcagagctat gctgtc           56


<210>  51
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  51
aagcaccgac tcggtgccac                                                   20


<210>  52
<211>  52
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  52
cactctttcc ctacacgacg ctcttccgat ctacatgcac acccatgttt tg               52


<210>  53
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  53
ggagttcaga cgtgtgctct tccgatctaa catttccagg tgacaggc                    48


<210>  54
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  54
cactctttcc ctacacgacg ctcttccgat ctgttccgac gctccttgaa                  50


<210>  55
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  55
ggagttcaga cgtgtgctct tccgatctca gatgcgatga cctttgtg                    48


<210>  56
<211>  52
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  56
cactctttcc ctacacgacg ctcttccgat ctaagaaagg caagaagcct gg               52


<210>  57
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  57
ggagttcaga cgtgtgctct tccgatctgc tggcctgaga cattccta                    48


<210>  58
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  58
tagccttatc tcaacttgct atgctgtcct gtttccagga cagcatagct ctgagac          57


<210>  59
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  59
taatacgact cactataggg gccactaggg acaggatgtc tcagagctat gcagtcc          57


<210>  60
<211>  60
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  60
cagtagcctt atctcaactt gctatgcagt cctgtttcca ggactgcata gctctgagac       60


<210>  61
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  61
ctgcctatac ggcagtagcc ttatctcaac ttgctatgca                             40


<210>  62
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  62
taatacgact cactatagct gccgtatagg caggtccgtt atcaacttga aaaagtg          57


<210>  63
<211>  43
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  63
aagcaccgac tcggtgccac tttttcaagt tgataacgga cct                         43


<210>  64
<211>  60
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  64
gtctagcctt atctcaactt gctatgcagt cctgtttcca ggactgcata gctctgagac       60


<210>  65
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  65
ctgcctatac ggcagtgtct agccttatct caacttgcta                             40


<210>  66
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  66
taatacgact cactatagct gccgtatagg cagagacagt ccgttatcaa cttgaaa          57


<210>  67
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  67
aagcaccgac tcggtgccac tttttcaagt tgataacgga ctgtctct                    48


<210>  68
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  68
guccguuauc aacuugaaaa aguggcaccg agucggugcu u                           41


<210>  69
<211>  32
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  69
gcaggacagc auagcaaguu gagauaaggc ua                                     32


<210>  70
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  70
ggggccacua gggacaggau gucucagagc uaugcugu                               38


<210>  71
<211>  82
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  71
ggggccacua gggacaggau gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuacug cc                                                82


<210>  72
<211>  82
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  72
guuuguguuu ccauaaacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuacug cc                                                82


<210>  73
<211>  82
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  73
gcccgccacc accaggaugu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuacug cc                                                82


<210>  74
<211>  82
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  74
ggcagccagc augaugagac gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuacug cc                                                82


<210>  75
<211>  46
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  75
ggcagguccg uuaucaacuu gaaaaagugg caccgagucg gugcuu                      46


<210>  76
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  76
ggggccacua gggacaggau gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuaguu cacugcc                                           87


<210>  77
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  77
guuuguguuu ccauaaacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuaguu cacugcc                                           87


<210>  78
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  78
gcccgccacc accaggaugu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuaguu cacugcc                                           87


<210>  79
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  79
ggcagccagc augaugagac gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuaguu cacugcc                                           87


<210>  80
<211>  68
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  80
gggcagugaa cuagccuuau cucaacuugc uaugcugucc uguuuccagg acagcauagc       60

ucugagac                                                                68


<210>  81
<211>  77
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  81
ggggccacua gggacaggau gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcua                                                      77


<210>  82
<211>  77
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  82
gcccgccacc accaggaugu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcua                                                      77


<210>  83
<211>  77
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  83
ggcagccagc augaugagac gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcua                                                      77


<210>  84
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  84
guccguuauc aacuugaaaa aguggcaccg agucggugcu u                           41


<210>  85
<211>  92
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  85
ggggccacua gggacaggau gucucagagc uaugcagucc uggaaacagg acugcauagc       60

aaguugagau aaggcuacug ccguauaggc ag                                     92


<210>  86
<211>  56
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  86
cugccguaua ggcagguccg uuaucaacuu gaaaaagugg caccgagucg gugcuu           56


<210>  87
<211>  96
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  87
ggggccacua gggacaggau gucucagagc uaugcagucc uggaaacagg acugcauagc       60

aaguugagau aaggcuagac acugccguau aggcag                                 96


<210>  88
<211>  61
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  88
cugccguaua ggcagagaca guccguuauc aacuugaaaa aguggcaccg agucggugcu       60

u                                                                       61


<210>  89
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Tet1-Spacer

<400>  89
ggctgctgtc agggagctca                                                   20


<210>  90
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Tet2-Spacer

<400>  90
gaaagtgcca acagatatcc                                                   20


<210>  91
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  91
tgtaagtcca ggatgaacta ggagaaa                                           27


<210>  92
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  92
tgttcaactt tagaacgaat acagaaa                                           27


<210>  93
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  93
agggtggggc aggaaggaag ccagaat                                           27


<210>  94
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  94
ctccctcagg gtctgtaaga aaagaaa                                           27


<210>  95
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  95
atacacccaa agtatcagga cgagaat                                           27


<210>  96
<211>  27
<212>  DNA
<213>  Homo sapiens

<400>  96
gcggtcgggg aataaggtat aaagaaa                                           27


<210>  97
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  97
uguaagucca ggaugaacua guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  98
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  98
uguucaacuu uagaacgaau guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  99
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  99
aggguggggc aggaaggaag guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  100
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  100
cucccucagg gucuguaaga guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  101
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  101
auacacccaa aguaucagga guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  102
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  102
gcggucgggg aauaagguau guuuuuguac ucgaaagaag cuacaaagau aaggcuucau       60

gccgaaauca acacccuguc auuuuauggc aggguguuu                              99


<210>  103
<211>  58
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  103
uguaagucca ggaugaacua guuuuuguac ucgaaagaag cuacaaagau aaggcuuc         58


<210>  104
<211>  54
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  104
uguucaacuu uagaacgaau guuuuuguac ucgaaagaag cuacaaagau aagg             54


<210>  105
<211>  58
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  105
aggguggggc aggaaggaag guuuuuguac ucgaaagaag cuacaaagau aaggcuuc         58


<210>  106
<211>  58
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  106
cucccucagg gucuguaaga guuuuuguac ucgaaagaag cuacaaagau aaggcuuc         58


<210>  107
<211>  58
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  107
auacacccaa aguaucagga guuuuuguac ucgaaagaag cuacaaagau aaggcuuc         58


<210>  108
<211>  54
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  108
gcggucgggg aauaagguau guuuuuguac ucgaaagaag cuacaaagau aagg             54


<210>  109
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  109
augccgaaau caacacccug ucauuuuaug gcaggguguu u                           41


<210>  110
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  110
tgtaaggaag ctgcagcacc agg                                               23


<210>  111
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  111
tctttgcctg gacaccccgt tc                                                22


<210>  112
<211>  118
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  112
agacccaaua ucaggagacu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau gaggcuaguc cguuaucaac uugaaaaagu ggcaccgagu cggugcuu        118


<210>  113
<211>  118
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  113
ugucccuagu ggccccacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau gaggcuaguc cguuaucaac uugaaaaagu ggcaccgagu cggugcuu        118


<210>  114
<211>  118
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas9-associated sgRNA

<400>  114
cggggacaca ggaucccugg gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau gaggcuaguc cguuaucaac uugaaaaagu ggcaccgagu cggugcuu        118


<210>  115
<211>  73
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  115
agacccaaua ucaggagacu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aag                                                          73


<210>  116
<211>  73
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  116
ugucccuagu ggccccacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aag                                                          73


<210>  117
<211>  73
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  117
cggggacaca ggaucccugg gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aag                                                          73


<210>  118
<211>  45
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  118
gcuaguccgu uaucaacuug aaaaaguggc accgagucgg ugcuu                       45


<210>  119
<211>  76
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  119
agacccaaua ucaggagacu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcu                                                       76


<210>  120
<211>  76
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  120
ugucccuagu ggccccacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcu                                                       76


<210>  121
<211>  76
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  121
cggggacaca ggaucccugg gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcu                                                       76


<210>  122
<211>  43
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  122
gaguccguua ucaacuugaa aaaguggcac cgagucggug cuu                         43


<210>  123
<211>  78
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  123
agacccaaua ucaggagacu gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuag                                                     78


<210>  124
<211>  78
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  124
ugucccuagu ggccccacug gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuag                                                     78


<210>  125
<211>  78
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  125
cggggacaca ggaucccugg gucucagagc uaugcugucc uggaaacagg acagcauagc       60

aaguugagau aaggcuag                                                     78


<210>  126
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Split-nexus Cas9-associated RNA

<400>  126
guccguuauc aacuugaaaa aguggcaccg agucggugcu u                           41


<210>  127
<211>  1387
<212>  PRT
<213>  Streptococcus pyogenes

<400>  127

Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
                165                 170                 175     


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
        195                 200                 205             


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
                245                 250                 255     


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
545                 550                 555                 560 


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


Gly Ser  Pro Lys Lys Lys Arg  Lys Val Glu Asp Pro  Lys Lys Lys 
    1370                 1375                 1380             


Arg Lys  Val Asp 
    1385         


<210>  128
<211>  1168
<212>  PRT
<213>  Streptococcus thermophilus

<400>  128

Met Pro Lys Lys Lys Arg Lys Val Asp Gly Ser Asp Leu Val Leu Gly 
1               5                   10                  15      


Leu Asp Ile Gly Ile Gly Ser Val Gly Val Gly Ile Leu Asn Lys Val 
            20                  25                  30          


Thr Gly Glu Ile Ile His Lys Asn Ser Arg Ile Phe Pro Ala Ala Gln 
        35                  40                  45              


Ala Glu Asn Asn Leu Val Arg Arg Thr Asn Arg Gln Gly Arg Arg Leu 
    50                  55                  60                  


Thr Arg Arg Lys Lys His Arg Arg Val Arg Leu Asn Arg Leu Phe Glu 
65                  70                  75                  80  


Glu Ser Gly Leu Ile Thr Asp Phe Thr Lys Ile Ser Ile Asn Leu Asn 
                85                  90                  95      


Pro Tyr Gln Leu Arg Val Lys Gly Leu Thr Asp Glu Leu Ser Asn Glu 
            100                 105                 110         


Glu Leu Phe Ile Ala Leu Lys Asn Met Val Lys His Arg Gly Ile Ser 
        115                 120                 125             


Tyr Leu Asp Asp Ala Ser Asp Asp Gly Asn Ser Ser Val Gly Asp Tyr 
    130                 135                 140                 


Ala Gln Ile Val Lys Glu Asn Ser Lys Gln Leu Glu Thr Lys Thr Pro 
145                 150                 155                 160 


Gly Gln Ile Gln Leu Glu Arg Tyr Gln Thr Tyr Gly Gln Leu Arg Gly 
                165                 170                 175     


Asp Phe Thr Val Glu Lys Asp Gly Lys Lys His Arg Leu Ile Asn Val 
            180                 185                 190         


Phe Pro Thr Ser Ala Tyr Arg Ser Glu Ala Leu Arg Ile Leu Gln Thr 
        195                 200                 205             


Gln Gln Glu Phe Asn Pro Gln Ile Thr Asp Glu Phe Ile Asn Arg Tyr 
    210                 215                 220                 


Leu Glu Ile Leu Thr Gly Lys Arg Lys Tyr Tyr His Gly Pro Gly Asn 
225                 230                 235                 240 


Glu Lys Ser Arg Thr Asp Tyr Gly Arg Tyr Arg Thr Ser Gly Glu Thr 
                245                 250                 255     


Leu Asp Asn Ile Phe Gly Ile Leu Ile Gly Lys Cys Thr Phe Tyr Pro 
            260                 265                 270         


Asp Glu Phe Arg Ala Ala Lys Ala Ser Tyr Thr Ala Gln Glu Phe Asn 
        275                 280                 285             


Leu Leu Asn Asp Leu Asn Asn Leu Thr Val Pro Thr Glu Thr Lys Lys 
    290                 295                 300                 


Leu Ser Lys Glu Gln Lys Asn Gln Ile Ile Asn Tyr Val Lys Asn Glu 
305                 310                 315                 320 


Lys Ala Met Gly Pro Ala Lys Leu Phe Lys Tyr Ile Ala Lys Leu Leu 
                325                 330                 335     


Ser Cys Asp Val Ala Asp Ile Lys Gly Tyr Arg Ile Asp Lys Ser Gly 
            340                 345                 350         


Lys Ala Glu Ile His Thr Phe Glu Ala Tyr Arg Lys Met Lys Thr Leu 
        355                 360                 365             


Glu Thr Leu Asp Ile Glu Gln Met Asp Arg Glu Thr Leu Asp Lys Leu 
    370                 375                 380                 


Ala Tyr Val Leu Thr Leu Asn Thr Glu Arg Glu Gly Ile Gln Glu Ala 
385                 390                 395                 400 


Leu Glu His Glu Phe Ala Asp Gly Ser Phe Ser Gln Lys Gln Val Asp 
                405                 410                 415     


Glu Leu Val Gln Phe Arg Lys Ala Asn Ser Ser Ile Phe Gly Lys Gly 
            420                 425                 430         


Trp His Asn Phe Ser Val Lys Leu Met Met Glu Leu Ile Pro Glu Leu 
        435                 440                 445             


Tyr Glu Thr Ser Glu Glu Gln Met Thr Ile Leu Thr Arg Leu Gly Lys 
    450                 455                 460                 


Gln Lys Thr Thr Ser Ser Ser Asn Lys Thr Lys Tyr Ile Asp Glu Lys 
465                 470                 475                 480 


Leu Leu Thr Glu Glu Ile Tyr Asn Pro Val Val Ala Lys Ser Val Arg 
                485                 490                 495     


Gln Ala Ile Lys Ile Val Asn Ala Ala Ile Lys Glu Tyr Gly Asp Phe 
            500                 505                 510         


Asp Asn Ile Val Ile Glu Met Ala Arg Glu Thr Asn Glu Asp Asp Glu 
        515                 520                 525             


Lys Lys Ala Ile Gln Lys Ile Gln Lys Ala Asn Lys Asp Glu Lys Asp 
    530                 535                 540                 


Ala Ala Met Leu Lys Ala Ala Asn Gln Tyr Asn Gly Lys Ala Glu Leu 
545                 550                 555                 560 


Pro His Ser Val Phe His Gly His Lys Gln Leu Ala Thr Lys Ile Arg 
                565                 570                 575     


Leu Trp His Gln Gln Gly Glu Arg Cys Leu Tyr Thr Gly Lys Thr Ile 
            580                 585                 590         


Ser Ile His Asp Leu Ile Asn Asn Ser Asn Gln Phe Glu Val Asp His 
        595                 600                 605             


Ile Leu Pro Leu Ser Ile Thr Phe Asp Asp Ser Leu Ala Asn Lys Val 
    610                 615                 620                 


Leu Val Tyr Ala Thr Ala Asn Gln Glu Lys Gly Gln Arg Thr Pro Tyr 
625                 630                 635                 640 


Gln Ala Leu Asp Ser Met Asp Asp Ala Trp Ser Phe Arg Glu Leu Lys 
                645                 650                 655     


Ala Phe Val Arg Glu Ser Lys Thr Leu Ser Asn Lys Lys Lys Glu Tyr 
            660                 665                 670         


Leu Leu Thr Glu Glu Asp Ile Ser Lys Phe Asp Val Arg Lys Lys Phe 
        675                 680                 685             


Ile Glu Arg Asn Leu Val Asp Thr Arg Tyr Ala Ser Arg Val Val Leu 
    690                 695                 700                 


Asn Ala Leu Gln Glu His Phe Arg Ala His Lys Ile Asp Thr Lys Val 
705                 710                 715                 720 


Ser Val Val Arg Gly Gln Phe Thr Ser Gln Leu Arg Arg His Trp Gly 
                725                 730                 735     


Ile Glu Lys Thr Arg Asp Thr Tyr His His His Ala Val Asp Ala Leu 
            740                 745                 750         


Ile Ile Ala Ala Ser Ser Gln Leu Asn Leu Trp Lys Lys Gln Lys Asn 
        755                 760                 765             


Thr Leu Val Ser Tyr Ser Glu Asp Gln Leu Leu Asp Ile Glu Thr Gly 
    770                 775                 780                 


Glu Leu Ile Ser Asp Asp Glu Tyr Lys Glu Ser Val Phe Lys Ala Pro 
785                 790                 795                 800 


Tyr Gln His Phe Val Asp Thr Leu Lys Ser Lys Glu Phe Glu Asp Ser 
                805                 810                 815     


Ile Leu Phe Ser Tyr Gln Val Asp Ser Lys Phe Asn Arg Lys Ile Ser 
            820                 825                 830         


Asp Ala Thr Ile Tyr Ala Thr Arg Gln Ala Lys Val Gly Lys Asp Lys 
        835                 840                 845             


Ala Asp Glu Thr Tyr Val Leu Gly Lys Ile Lys Asp Ile Tyr Thr Gln 
    850                 855                 860                 


Asp Gly Tyr Asp Ala Phe Met Lys Ile Tyr Lys Lys Asp Lys Ser Lys 
865                 870                 875                 880 


Phe Leu Met Tyr Arg His Asp Pro Gln Thr Phe Glu Lys Val Ile Glu 
                885                 890                 895     


Pro Ile Leu Glu Asn Tyr Pro Asn Lys Gln Ile Asn Glu Lys Gly Lys 
            900                 905                 910         


Glu Val Pro Cys Asn Pro Phe Leu Lys Tyr Lys Glu Glu His Gly Tyr 
        915                 920                 925             


Ile Arg Lys Tyr Ser Lys Lys Gly Asn Gly Pro Glu Ile Lys Ser Leu 
    930                 935                 940                 


Lys Tyr Tyr Asp Ser Lys Leu Gly Asn His Ile Asp Ile Thr Pro Lys 
945                 950                 955                 960 


Asp Ser Asn Asn Lys Val Val Leu Gln Ser Val Ser Pro Trp Arg Ala 
                965                 970                 975     


Asp Val Tyr Phe Asn Lys Thr Thr Gly Lys Tyr Glu Ile Leu Gly Leu 
            980                 985                 990         


Lys Tyr Ala Asp Leu Gln Phe Glu  Lys Gly Thr Gly Thr  Tyr Lys Ile 
        995                 1000                 1005             


Ser Gln  Glu Lys Tyr Asn Asp  Ile Lys Lys Lys Glu  Gly Val Asp 
    1010                 1015                 1020             


Ser Asp  Ser Glu Phe Lys Phe  Thr Leu Tyr Lys Asn  Asp Leu Leu 
    1025                 1030                 1035             


Leu Val  Lys Asp Thr Glu Thr  Lys Glu Gln Gln Leu  Phe Arg Phe 
    1040                 1045                 1050             


Leu Ser  Arg Thr Met Pro Lys  Gln Lys His Tyr Val  Glu Leu Lys 
    1055                 1060                 1065             


Pro Tyr  Asp Lys Gln Lys Phe  Glu Gly Gly Glu Ala  Leu Ile Lys 
    1070                 1075                 1080             


Val Leu  Gly Asn Val Ala Asn  Ser Gly Gln Cys Lys  Lys Gly Leu 
    1085                 1090                 1095             


Gly Lys  Ser Asn Ile Ser Ile  Tyr Lys Val Arg Thr  Asp Val Leu 
    1100                 1105                 1110             


Gly Asn  Gln His Ile Ile Lys  Asn Glu Gly Asp Lys  Pro Lys Leu 
    1115                 1120                 1125             


Asp Phe  Gly Ser Ala Tyr Pro  Tyr Asp Val Pro Asp  Tyr Ala Ser 
    1130                 1135                 1140             


Leu Gly  Ser Gly Ser Pro Lys  Lys Lys Arg Lys Val  Asp Gly Ser 
    1145                 1150                 1155             


Pro Lys  Lys Lys Arg Lys Val  Asp Ser Gly 
    1160                 1165             


